Evolving role of Sorafenib in the management of hepatocellular carcinoma

Ziogas, Ioannis A.; Tsoulfas, Georgios

doi:10.5306/wjco.v8.i3.203

Cited by 36 publications

(42 citation statements)

References 104 publications

(121 reference statements)

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“…As liver resection represents the mainstay of treatment in non-metastatic HCC [32][33][34] , several studies aimed to investigate the difference in outcomes between young and old HCC patients. Therefore, data have proven the safety and feasibility of liver resection in appropriately selected patients aged not only more than 70 years, but, in some cases, even more than 80 years [35][36][37][38] .…”

Section: Liver Resection and Agementioning

confidence: 99%

Frailty and Liver resection: where do we stand?

Sioutas¹,

Ziogas²,

Tsoulfas³

2020

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As the world population is continuously aging, the number of older patients requiring liver surgery is also on the rise. Data have shown that age should not be a limiting factor for liver resection, as it cannot accurately predict postoperative outcomes. Instead, frailty can serve as a more reliable measure of the patient's overall health and functional reserves. Several frailty assessment tools have been implemented for preoperative risk stratification before liver surgery, and higher scores have commonly been associated with postoperative morbidity, mortality, and length of hospital stay. However, no consensus has been reached on the most useful screening tool. Future studies should focus on comparing the currently available assessment tools, constructing a liver resection-specific tool, and assessing the role of frailty assessment tools in preoperative patient optimization.

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Section: Liver Resection and Agementioning

confidence: 99%

Frailty and Liver resection: where do we stand?

Sioutas¹,

Ziogas²,

Tsoulfas³

2020

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“…Patients with more advanced stages (stages C and D of the BCLC classification) have more limited and less effective therapeutic options [5, 9, 10]. In recent years, there has been a breakthrough in the knowledge of the molecular pathogenesis of HCC, which has led to the development of molecular targeted therapies such as sorafenib [4, 6, 11, 12].…”

Section: Introductionmentioning

confidence: 99%

“…Treatment options for HCC depend on the stage of the disease, and surgical resection, hepatic transplantation, ablation or chemoembolization are recommended in the early stages (stages A and B of the Barcelona Clinic for Liver Cancer [BCLC] classification) [5, 9, 10]. Patients with more advanced stages (stages C and D of the BCLC classification) have more limited and less effective therapeutic options [5, 9, 10].…”

Section: Introductionmentioning

confidence: 99%

“…In recent years, there has been a breakthrough in the knowledge of the molecular pathogenesis of HCC, which has led to the development of molecular targeted therapies such as sorafenib [4, 6, 11, 12]. This drug is a multikinase inhibitor, active against the Raf-1 serine/threonine protein-kinase proto-oncogene and the B-Raf proto-oncogene, the vascular endothelial growth factor receptor cells 1–3, platelet-derived growth factor receptor β, as well as the gene fms-related tyrosine kinase 3, RET gene, c-KIT gene, stimulating apoptosis, and inhibiting the proliferation and angiogenesis of tumor cells [4, 5, 9, 13-16]. Currently, sorafenib is recommended in advanced HCC, and its effect on increasing the median overall survival of these patients has been demonstrated in approximately 3 months [5, 9, 12-15, 17].…”

Section: Introductionmentioning

confidence: 99%

“…This drug is a multikinase inhibitor, active against the Raf-1 serine/threonine protein-kinase proto-oncogene and the B-Raf proto-oncogene, the vascular endothelial growth factor receptor cells 1–3, platelet-derived growth factor receptor β, as well as the gene fms-related tyrosine kinase 3, RET gene, c-KIT gene, stimulating apoptosis, and inhibiting the proliferation and angiogenesis of tumor cells [4, 5, 9, 13-16]. Currently, sorafenib is recommended in advanced HCC, and its effect on increasing the median overall survival of these patients has been demonstrated in approximately 3 months [5, 9, 12-15, 17]. Sorafenib therapy is generally indicated in patients with BCLC stage B refractory to locoregional therapies or who have contraindications to its use, as well as in selected BCLC stage C patients [4, 13].…”

Section: Introductionmentioning

confidence: 99%

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Perfusion Magnetic Resonance as a Biomarker for Sorafenib-Treated Advanced Hepatocellular Carcinoma: A Pilot Study

Campos

Candelária

Papanikolaou

et al. 2019

GE Port J Gastroenterol

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Background: Sorafenib is the currently recommended therapy in patients with advanced hepatocellular carcinoma (HCC). Among the several biomarkers available for the evaluation of the therapeutic response and prognosis, there is perfusion magnetic resonance imaging (p-MRI) that, through measurement of the vascular permeability unit (ktrans), may retrieve useful information regarding the microvascular properties of focal liver lesions. The aim of this study was to evaluate the impact of sorafenib therapy in patients with advanced HCC using the p-MRI technique. Materials and Methods: In this retrospective study, 27 patients with the diagnosis of advanced HCC were included for palliative therapy using sorafenib. MRI of the liver was performed before the beginning of the oral therapy (T0), after 3 (T3), and after 6 months (T6). Dynamic acquisitions of the tumor (n = 50, during the first 2 min after contrast injection) were obtained in the coronal plane and were used to compute the parametric perfusion maps, acquiring the ktrans value using the extended Tofts pharmacokinetic model. Results: The value of ktrans obtained at T0 was significantly different from the value of ktrans obtained at T6 (p = 0.028). There were no significant differences between T0 and T3 (p = 0.115) or a correlation between ktrans at T0 and the size of the lesion (p = 0.376). The ktrans value at T0 in patients with progression-free survival (PFS) > 6 months was not significantly different from the ktrans value in patients with PFS ≤6 months (p = 0.113). The ktrans value at T0 was not significantly different between patients who were previously submitted to chemoembolization and those who were not submitted (p = 0.587). Conclusion: In this pilot study, the ktrans value may serve as a biomarker of tumor response to antiangiogenic therapy, but only 6 months after its initiation. Clinical outcomes such as PFS were not predicted before the initiation of treatment.

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Combination therapy of sorafenib with mesenchymal stem cells as a novel cancer treatment regimen in xenograft models of hepatocellular carcinoma

Seyhoun

Hajighasemlou

Muhammadnejad

et al. 2018

Journal Cellular Physiology

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Aim Hepatocellular carcinoma (HCC) is the most common liver malignancy and the second leading cause of cancer‐related deaths in the world. Sorafenib is the first‐line treatment of HCC. Although sorafenib has positive effects on the survival of patients, novel therapeutic strategies are needed to extend survival and improve the efficacy of sorafenib. This study combines sorafenib with mesenchymal stem cells (MSCs) as a new approach to enhance the efficacy of sorafenib. Material and methods A subcutaneous xenograft model of HCC, established by human HepG2 cell lines, was implanted into the flank of nude mice and was used to evaluate tumor growth after treatment with sorafenib alone or in combination with MSCs. The aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and creatinine levels were measured for safety assessment. Histopathological studies were performed using hematoxylin and eosin staining, and immunohistochemistry tests were performed to evaluate proliferation (Ki67) and angiogenesis (CD34). The TUNEL assay was used to detect apoptosis and measure the expression of major inflammatory cytokines (IL‐1a, IL‐10, and TNF‐α) with real‐time polymerase chain reaction. Result Sorafenib, in combination with MSCs, strongly inhibited tumor growth in the xenograft model. Furthermore, the combination therapy significantly inhibited HCC cell proliferation, decreased tumor angiogenesis, and induced apoptosis and maintained antitumor‐associated anti‐inflammatory effects of MSCs. Conclusion This combination therapy strategy could be used as a new therapeutic approach to the treatment of HCC that significantly improves upon the results achieved using sorafenib as monotherapy.

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Evolving role of Sorafenib in the management of hepatocellular carcinoma

Cited by 36 publications

References 104 publications

Frailty and Liver resection: where do we stand?

Frailty and Liver resection: where do we stand?

Perfusion Magnetic Resonance as a Biomarker for Sorafenib-Treated Advanced Hepatocellular Carcinoma: A Pilot Study

Combination therapy of sorafenib with mesenchymal stem cells as a novel cancer treatment regimen in xenograft models of hepatocellular carcinoma

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